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21




KG-135
&




         1
CONTENTS




                                                                                                        13
           21


                                           KG-135
                                     &                                                                  15         Agape Medicine
             2011
           All rights reserved. No part of this publication may be reproduced, stored in a retrieval
           system, or transmitted, in any form or by any means, electronic, mechanical, photocopying,
           recording, or otherwise, without the prior written permission of the publisher.              17
           Printed in Taiwan.




                                                                                                        19
                        KG-135           &
                                       2011.05
           192    21X15
           ISBN 978–986–6552–86–1
           1.      2.       3.
           414.34 100008505

      主編   詹治東
      監修   詹瑩璽
      審訂   朴萬基、朴政一
    出版發行   唐山出版社|Tonsan Publications Inc.                                                               23
           10647 臺北市大安區羅斯福路三段333巷9號B1
           tel 02–2363–3072
           fax 02–2363–9735
           tonsan@ms37.hinet.net
           http://blog.yam.com/tsbooks/ 
    出版日期   2011.05
2     定價   NT $ 250                                                                                                                 3
Part   1        Part   2


    27              55   11




    31              57                7


                7



    34




    39              79                4


                                DNA




    47

4                                         5
Part   3                 116

                          KG-135

    85           KG-135
          KG-135



    89    KG-135
          KG-135

          KG-135

                                   124

    100   KG-135




          Part   4


    113



    115




6                                        7
Part   5
                     Q&A   176

                           177

    169



    170

                           178

    171

                           179




    172

                           180



    173                    181



                           182

    174

                           183




    175



8                                9
184



     185




     186




     187




     188




     189




     190



10         11
2010




12          13
Agape Medicine




                                             2008    1    1
         40-70




                 Agape Medicine




                                  4%      dark material
                 23%                        dark energy
                   73%
KG-135
&




                                                  Agape
14                                                            15
do no harm




         do harm
KG-135
&




16                              17
1995     9




                                       11




                                            50


                          40-70
KG-135




         10-30
                 70               10
&




18                                               19
20




                            2000   12
                10




         2005




                     2010
KG-135
&




20                                       21
Ginsenoside Rs3   Rs4   7
                                         Rk1
     Rg3   Rg5




22                                             23
1.   2.   3.
         4.

                             Part   1
KG-135
&




24                                      25
DNA




26         27
. D.                       Dr. Ernst. D. Prinzenberg




                                                Ginsenosides
                                 Ra1       Ra2 Ra3 Rb1 Rb2                Rb3     Rc
              Panaxdiolegroup
                                 Rd       Rg3     Rh2    Rs1     Rs2
                                                Ginsenosides
              Panaxtriolegroup   Re       Rf    Rg1     Rg2    Rh1     Rh 3

                                                Ginsenosides         Ro
              O leanolicacid
                   Phenoles                    Maltol


                                 B-12,folic acid, nicotine acid, pantothenic
                                 acid, biotin, nicthlamide



                                 Aspartic acid, blycine, alanine, praline,
                                 valine, isoleucine, tyrosine, phenylalanine,
                                 fatty amino acids, arginine
         20
                                 200
                   0.05%
KG-135
&




28                                                                                        29
/


         /   panax   panacea
KG-135
&




30                             31
1
         2
                 6000       300
         3
         4
         5
         6
         7
         8




                        7

             1
             2
             3
             4
             5
             6
KG-135




             7
&




32                                33
6




                       10




              36
         38
KG-135
&




34                          35
+           +++
                     +           +++
                     +           ++
                     +           ++
                     +           +++
                     +           ++
                     +           ++
                     +           +++
                     +           ++
KG-135




         3       4       5       6

         1.83%   2.09%   2.32%   3.43%

         1.59%   1.95%   2.30%   2.79%
&




36                                       37
*         M.Kiura
         *         W.Petkov
         *         J.Ishigami
         *   DNA   M.Yamamoto
         *         H.G. Chai
         *         I.Murata
                                                      1960
         *         S.Odashima
         *         H.Oura
         *         M.Yamamoto
         *         C.N. Joo
         *         B.H. Han
                                     I.I. Brekhman   1969
         *         S.J.Fulder
         *         E.V.Avakian
         *         E.Bombardelli
         *         D.J. Lee
         *         I.Murata
         *         M.Yonezawa
                   N.Saito
         *
                   Subhuti                  6%
         *
                   Dharemanda
         *
                   C.N. Joo
         *         J.B. Kim
KG-135




         *         H.Matsuda
         *         T.Saito
         *         V.D.Petkov
         *         O.Tanaka
&




         *         S.K.F.Chong
         *         Masao Haneda
38                 Shojvo Ikematsu                           39
40



                                                          R 3O
                                                          OH




                                      R 1O
                                                     R2



                                Ginsenoside       R1             R2           R3
                                   Rb1         Glc-Glc-          H         Glc-Glc-
                                   Rb2         Glc-Glc-          H        Ara(p)-Glc-
                                    Rc         Glc-Glc-          H        Ara(f)-Glc-
                                    Rd         Glc-Glc-          H           Glc-
                                   Rg3         Glc-Glc-          H            H
         100                        Rs3       Ac-Glc-Glc-        H            H
                                    Re            H          Rha-Glc-O-       H
               100   100           Rg1            H            Glc-O-        Glc-
                                   Rg2            H          Rha-Glc-O-       H
                                    Rf            H          Glc-Glc-O-       H
                                   Rh1            H            Glc-O-         H
KG-135
&




40                                                                                      41
Rg3             Ginsana


                10             Rg3




                                               1




                     Ginsana


         G115
                Pharmaton
                  Ginsana


                                               Ginsana
                                               1
KG-135
&




42                                                       43
Rh2   Rg3       Rk1




                                                     Rk1


                                                         Drug      Rk1          Taxol
                                      Cell line                   (μg/ml)       (μg/ml)

                                              SK-OV-3(卵巢癌細胞)    3.9 ± 0.80    2.3 ± 0.37
                                          NIH:OVCAR-3 (卵巢癌細胞)   18.9 ± 0.21   10.5 ± 3.58
                                             DU-145(攝護腺癌細胞)     21.0 ± 4.24   12.5 ± 2.12

                                              PC-3 (攝護腺癌細胞)     19.0 ± 2.83    4.0 ± 2.80

                                                  MCF-7(乳癌細胞)   24.0 ± 0.00   25.5 ± 0.71

                                              HL-60(骨髓性白血病)     5.2 ± 0.08    2.7 ± 0.46




         500                    1
KG-135




               37


         1                  1
&




44                                                                                          45
Saponin         37      22        14         15
                          7.47%   3.16%     2.09%      2.25%




         Rb1
         Rb1
         Rb1   Rc
         Rb1
         Rb1
         Rb
         Rg1   Rb1   Re                   DNA    RNA


         Rh2   Rh3   Rg3
         Rg2   Rh1   Rg3                                                       1995
         Rg1   Re    Rd
         Rg1                                                        11
         Rb1   Rb2   Rc    Re
KG-135




         Rg1
         Rb1
&




46                                                             5%        100          47
11


                                                    500




                                             70           10
                                            40-70          10-30




                     p.50 p.51




          5
         100                     5
               995
KG-135




                                 95%
&




48                                                                 49
1987
                                                1987-1989         NIH




                Northwestern University




         1977                                           University of Wisconsin-Madison




         1987        University of Pittsburgh   1986-1990 Wurzburg
KG-135




         1987                                   1993
&




                                                (   )
50                                                                                        51
         1987                                   2001
1
             Anti-oxidant activity                                                            SG
                                                  0.8
                         100                                                                  WG
                                                  0.6
                                      survival



                         80                       0.4


                                                  0.2


                                                                                                                  2
          % Inhibition




                         60
                                                   0                                                       Part
                                                        0     200    400         600    800   1000
                         40                                         Co n c .(mg /mL)



                         20


                          0
                               0    0.1            0.2       0.3    0.4       0.5      0.6    0.7
                                                        Concentration (mg/mL)


                                                   1
             Anti-cancer activity                                                             SG
                                                  0.8
                           1                                                                  WG
                                                  0.6
                                                                                              SG
                                      survival




                          0.8                     0.4


                                                  0.2
                                                                                              WG
                          0.6
         survival




                                                   0
                                                        0     200    400         600    800   1000

                          0.4                                       Co n c .(mg /mL)
KG-135




                          0.2
&




                           0
                                0                200          400          600         800          1000

                                                            Co n c .(mg /mL)
52                                                                                                                    53
11




          37
               26   11




54                       55
7
                   Major Constitunets
                   Ginsenoside Rk1      Rg3   Rg5
                   Unique Constituents
                   Ginsenoside Rk2      Rk3   Rg1
                   Ginsenoside Rs4      Rs5   Rs6   Rs7
                   Ginsenoside Rh2
                                                          11




         Rh2
         Rg3


         Rg1
                                        DNA RNA
         Rg5,Rk1
         Rs3,Rs4
         Rg3,Rg5
         Rk1
KG-135
&




56                                                                 57
Antioxidant Activitiy


                       DNA
                                        DNA




                                 解毒作用
KG-135




         1.
         2.
&




         3.
58       4.                                   59
Chemoprevention Activity
                         100



                          80



                          60
          % Inhibition




                          40                                         SG
                                                                     RG
                                                                     WG
                          20



                           0
                               0    2          4          6      8
                                   Concentration mg ginseng/mL

         J. Nat. Prod. 63, 1702 2000
         Cancer Letters 150, 41 2000
KG-135
&




60                                                                                                   61
致癌物



                       1~2 days                        1-



                                                              排出體外

                       >10 years   2-



                                                     1-解毒癌變物質
                  促進

                       >1 year
                             癌化前細胞
              4

                                                4-
         1.
         2.
         3.
                            腫瘤細胞 3-
KG-135




         4.
&




                                    Apoptosis
62                                                              63
Anticancer Activity
                     1


                    0.8
                                                                                      60~120
                    0.6                                              SG
         Survival




                                                                     RG
                    0.4
                                                                     WG

                    0.2


                     0
                          0   200      400      600     800   1000
                              Concentration mg ginseng/mL                 Rg3 Rg5 Rk1 Rs4         Rh2
                                                                                      Apoptosis         Rg3 Rg5   Rk1
         Cancer Letters 150, 41 2000
         Anticancer Research 19, 487 1999
         Anticancer Research 17, 1067 1997




                                    apoptosis
KG-135
&




64                                                                                                                      65
Control                                           DMBA + TPA




                                300mg/kg
                                                                                                               22




                                            0           1           2                     3               22 weeks




                                           DMBA               TPA       TPA   TPA   TPA       TPA   TPA        TPA   TPA




                                                Initiation                          Promotion
KG-135




                                                                                     DMBA + TPA



             HL60
&




         -
         -          100 mg/kg
         -          300 mg/kg
66                                                                                                                          67
Vascular, relaxation activity                                                           90.0

                                                  SG
                                                                                                 80.0

                                                  RG                                             70.0

                                                  WG                                             60.0
                                                                                                 50.0
                                                                                                 40.0
                                                                                                 30.0
                                                                                                 20.0
                                                                                                 10.0
                                                                                                 0.0
                                         5.5     5.0     4.5     4.0      3.5        3.0   2.5
                                                                conc. (-log C)


                                         J. Nat. Prod. 63,1702 2000
                                         Eur. J. Pharmacology 367, 41 1999 51 1999
                                         Advances in Ginseng Res. 182 1998
KG-135
&




68                                                                                                      69
Rg3        Rg5        Rk1
                                                                          Kidney protection activity


                                                                                                       1.5




                             150

                             120
         Swimming time min




                              90

                              60
KG-135




                              30

                               0
                                   Control               +Ginseng
&




                                         Swimming test
70                                                                                                           71
100 mg/kg/day,   ,


                                                                                              1300        1240
                                                                                              1200
                                                                                              1100                    1040




                                                                               Tumor size
                                                                               Tumor size
                                                                                              1000
                                                                                                                             890
                                                                                              900
         Cisplatin
                                                                                              800
                                                                                                                                       690
           Cisplatin                                                     BUN                  700
         Creatinine                                                                           600
                                                                                              500

                                                                                                                                   +




                                                                                                     100 mg/kg/day,   ,

                                                                                               90

                                                                                               85

                                                                                               80
             Blood cholesterol level mg/dl




                                             1000




                                                                               Survival day
                                                                                               75


                                              800                                              70

                                                                                               65

                                              600                                              60
KG-135




                                                                                               55
                                              400
                                                                                               50

                                              200                                              45
&




                                                                                               40
                                                0
                                                    Control   +Ginseng
                                                                                                                                   +
72                                                                                                                                           73
Anti-platelet Aggregation



                                         4

                                        3.5
                                                                                                                             Rg3
                                         3

                                        2.5

                                         2

                                        1.5

                                         1

                                        0.5

                                         0
                            +                 control   cisplatin cisplatin
                                                                     +
                                                                     선삼       Rg3

         Korean Patent 1998-033461 1998-08-18




                                                                              Biological Pharmaceutical Bull., 21, 79 1998
                                                                              Korean J. Ginsengscience, 21, 132 1997
KG-135
&




                                                                                           Rg3

74                                                                                                                                 75
Brain Cell Protection Activity
                                          Water maze experiment
                                          20 mg/kg, p.o. 7th day

                                                    40
                                                    35
                                                    30
                                                    25
                                                    20
                                                    15
                                                    10
                                                      5
                                                      0
                                                              Control        SG




                                          Passive avoidance test
                                          5 mg/kg,     , 7th day
                           SOD
                                                   250

                                                   200

                                                   150
KG-135




                                                   100

                                                     50
&




                                                      0
                                                            Control     SG    Rg3
76                                                                                  77
100
                                                                4
         70                         50    20   10




         Acetylcholine


                                    9
                                    8
                                    7
              Concentration ng/mg




                                    6
                                    5
                                    4
                                    3
                                    2
                                    1
                                    0
                                         Control           鉆葚
KG-135




         After oral administration for 7 days, 50 mg/kg.
         Acetylcholine concentration in Hippocampus
&




78                                                                  79
DNA


         99.5%




                                                    Saponin
                                   soap
                             DNA
                       92%




                                               30             50
                                          70
KG-135
&




80                                                                 81
Part   3

     KG-135




82               83
KG-135




            KG-135


                                                     KG-135
     KG135       Rk1 Rg3            Rg5




     HPLC data
                     Rg1,Re   Rb1   Rb2
                                     Rd
     White
     Ginsneg
                                          Rc




     Red
     Ginseng




                                               Rg3   Rk1   Rg5

     S.G.




                                                                 KG-135
84                                                               85
KG-135


                                                                                                                                                           1.4

                                                                                                                                                           1.2
                                                                                                                               KG-135
                                                                                                                                                            1                       Rg3
                                                                                              Rg3
                                                                                                                    Rg5
                                                                                                                                                                                         Rg5




                                                                                                                                                survival
                                                                                                                    Rk1                                    0.8
                                                                                                                                                                                           Rk1
                                                                                                                                                           0.6

                                 MTT
                                                                                                                                                           0.4
                    1.2000


                                                                                                                                                           0.2
                    1.0000



                    0.8000
                                                                                                                                                            0
                                                                                                                                                                 0        20        40           60    80   100
                    0.6000

                                                                                                                                                                               Concentration (mg/mL)
                                                                                                                                                                                             (mg/mL)
         Survival




                    0.4000



                    0.2000


                                                                                                         Rs3             Rs4, Rs5
                    0.0000
                          0.00   2.75   5.50   8.25 11.00 13.75 16.50 19.25 22.00 24.75 27.50 30.25 33.00 35.75 38.50 41.25 44.00 46.75 49.50


                                                                                                                             Time min.
                             HPLC separation – Fraction collection – MTT assay
KG-135
&




                                                                                                                                                                                                                  KG-135
86                                                                                                                                                                   KG-135                                       87
KG-135
         CH2      CH CH        (C C)2   (X)   (CH2)6CH3
                           R                          Polyacetylene


            O


                      OH           HO
                                  OH                                    KG-135
            O
         Maltol
                                                    Ginsenoside Rg3



         Glc    Glc   O




                                                    Ginsenoside Rg5
KG-135




                                  OH



                                                    Ginsenoside Rk1
&




                                                                                 KG-135
         Glc    Glc   O
88                                                                               89
PC-3
                         Morphology of PC-3 SP cells




                         200 X                                                      400 X
         KG-135   PC-3
                                                                                         PC- 3




                         KG-135       PC-3
                         Effect of KG135 on cell viability of PC-3 prostate cells



                                                           100
                                                                                                                24 h




                           Cell viability (% of control)
                                                                                                                48 h
                                                            80                                                  72 h



                                                            60



                                                            40
KG-135




                                                            20



                                                             0
&




                                                                 0   2   5    10    20      40   50   60   80     100




                                                                                                                        KG-135
                                                                             Concentration (mg/ml)

90                                                                                                                      91
KG-135         PC- 3                                           KG135 inhibited PC-3 cell migration
         Effects of KG135 on side population of PC-3 prostate cells




                                                                      Control




                                                                                               5 g/ml KG135
               1.1%                          0.4%




                                                                                                                KG135
                                                                                                                PC – 3
                                                                                               7.5 g/ml KG135
                                                                      +25 mM Verapamil
                                             0.2%




                                                                                               10 g/ml KG135
          Side population
                      1.1 %  5




                                                                      + 25 mM Reserpine
         mg/ml KG-135       0%
                    KG-135
                                             0%
KG-135
&




                                                                                                                         KG-135
92                                                                                                                       93
KG-135




                                                                              Apoptosis


                                                                            KG-135        Apoptosis




                                                                                Autophagy
KG-135
&




                                                                                                      KG-135
94         http://www.nature.com/onc/journal/v23/n16/images/1207521f4.jpg                             95
Apoptosis inducing effect of KG-135                                                                        KG-135
                                                                            Hydroxychloroquine                  A549

         SKOV-3




                                                                            Western blot ananysis of A549 human lung cancer cells
                                                                            treated with KG135 for 72 h
                            4.88%                                  27.55%
                                                 6.44%
                                                                                                           KG 135    g/ml
                                                                                                 Control   50       75      100
                  Control
                  Control            10 m
                                      10 g/ml
                                          g/ml           30 30mg/ml
                                                             g/ml
                                                                                         FAK
                                                                                                                                  KG135     A549
                                                                                        p-FAK


                                                                                          Akt

         NIH:OVCAR3
                                                                            LC3-II
                                                                            LC3-I       LC3-I                                             KG-135
                                                                                        LC3-II



                            10.03%                                  29.04
                                               14.18%
                                                                    %                 GAPDH
KG-135




              Control                10 g/ml             20 g/ml
&




                                                                                                                                                   KG-135
96                                                                                                                                                 97
Western blot ananysis of A549 human lung cancer cells                    3
                  treated with KG135 for 72 h                                   A549 lung cancer cells 3 days of treatment A549

               KG135 50 g/ml
                                                              KG135
     Hydroxychloroquine 25 M

                                                              A549
                           FAK


                       p-FAK


                            Akt
                                                                           Control                        KG135 75 g/ml

         LC3-II
         LC3-I            LC3-I
                                                                  KG-135
                          LC3-II




                      GAPDH




                                                                           H-CQ 25                        KG135 75 g/ml+H-CQ 25 M
KG-135
&




                                                                                                                                           KG-135
                  KG135
98                                 A549                                                                                           KG-135   99
KG-135                                      DBTRG 05MG glioblastoma cells 72 h treatment


                                                                                    H-CQ




           KG-135       Hydroxychloroquine
         DBTRG05MG


                      KG-135    Hydroxychloroquine   KG135
              DBTRG05MG                                         DBTRG 05MG




                                                     DBTRG 05MG glioblastoma cells 72 h treatment



                                                                             H-CQ
KG-135
&




                                                     KG135




                                                                                                    KG-135
                                                                DBTRG 05MG

100                  KG-135                                                                         101
KG-135            matformin           KG-135
           A549

                                                             Chemoprevention activity
                            KG-135      matformin
                   A549
   01/24




                                                                                DMBA + TPA




                                                                                DMBA + TPA+
                                                                                 100 mg


           KG135   metformin
                         A549
KG-135




                                                                                DMBA + TPA+
                                                                                 500 mg
&




                                                                                              KG-135
102                                                                                           103
KG-135 Standardized SG extract inhibits TPA-                    Effects of KG-135 on phorbol ester-induced cox-2
                 induced COX-2 expression in human breast epithelial             expression and ERK activation in mouse skin
                   MCF-10A cells.
                                                                                                                                   + KG-135 mg/kg
                                                                                                                               0         100      500
                                   KG-135
                                                                                                             Control
                                                                                                                                         + TPA
                             TPA

         COX-2                                                                   COX-2




         Actin
                                                                                 Actin




                                                                                 pERK

                                   KG-135
                                       TPA
         COX-2                                                                   ERK




         Gapdh


                                                                                         KG-135 inhibits cox-2 expression and ERK activation


                 KG-135 inhibits TPA-induced cox-2 expression in MCF-10A cells
KG-135




                                                                                   COX-2 + TPA



                    COX-2 + TPA                                                                                                    KG-135
&




                                                                                                                                                        KG-135
                                                                     KG-135

104                                                                                                                                                     105
Effect of KG-135 on TPA-Induced Subsequent
         Degradation of Icy-a, and on NF-kB DNA Binding in
         Mouse Skin Treated with TPA
                                                                                              120
                                            + KG-135 mg/kg
                                        0         100      500
                                                                                              100
                          Control
                                                 + TPA




                                                                         % Mice with tumors
                                                                                                                                Control

         IkB-a                                                                                 80                                              Control+SG 100mg/kg


                                                                                               60

                                                                                                                                                  Control+SG 500mg/kg
             IkB-a                                                                             40



                                                                                               20


                                                                                                                                                      Control_negative
         Actin                                                                                  0
                                                                                                    1   2   3   4   5   6   7   8   9     10 11 12 13 14 15 16 17 18     Weeks




         IkB-a
         NF-kB                                           TPA +
                                    Co only




                                                      KG-135(mg/kg)
                                            l
                                         ro




                                                                    p.
                                          e




                                                  A
                                       ob

                                       nt




                                                                   m
                                                TP




                                                                0




         KG-135
                                                        0



                                                                 Co
                                                              50
                                    Pr




                                                      10
KG-135




                                                 NF-kB
&




                                                                                                                                                                                 KG-135
106                                                                                                                                                                              107
KG-135 SG-unique constituents inhibits COX-2 expression           KG-135 inhibits BrDU and PCNA in vivo
         by blocking the activation of JNK and AP-1 in phorbol ester-
                                                                                                              DMBA + TPA
         stimulated human breast epithelial cells.
                                                                                                        KG-135          KG-135
                                                                        Control Acetone   DMBA + TPA   100mg/kg        500mg/kg



                       KG-135
                 TPA

                JNK




         JNK


                                                                        BrDU
                 KG-135
                 KG-135                JNK



                 KG-135
                 KG-135
                                       on obe




                                KG-135       -   -         +
                                                           pr ld
                                                                e
                                         pr
                                         ly




                                                             ob


                                 TPA         -             -
                                                             co



                                                 +   + +


                                AP-1                                    PCNA
                                激活蛋
                                白
KG-135
&




                                                                                                                                  KG-135
108                                                                                                                               109
100
                                                  DMBA-TPA

                                80                + 0.1% SG
         % Tumor bearing mice




                                60
                                                  + 0.5% SG
                                                                                                   Part   4
                                40



                                20



                                 0
                                      0   2   4      6    8   10   12   14   16   18   20     22

                                                                                            Week

         Cancer Letters, 150, 41 2000
         Topical application of SG 10 min prior to TPA application
KG-135
&




110                                                                                                           111
1.
      2.
      3.




112        113
1.


         2.
         3.




              2005
KG-135
&




114                  115
100mg    200mg
                               5~7
              250mg
              250mg
              500 mg
              1000mg




         15
KG-135
&




116                                  117
KG-135




         3
&




118          119
11.


               12.

         1.
               13.
               14.

         2.

               15.
         3.

               16.


               17.
         4.
               18.


               19.
         5.



               20.
         6.

               21.
         7.
               22.

         8.
               23.

         9.
KG-135




               45.

         10:
               25.
&




               26.

120                  121
27.   42.


         28.   43.


         29.
               44.


         30.
               45.   /


         31.



         32.


         33.


         34.
         35.


         36.


         37.


         38.
KG-135




         39.


         40.
&




         41.

122                      123
54




          60




                    55




         76
KG-135




                         1000
               mg
&




124                             125
59


                                             15
                                       1000 mg
                             25                                                  1500 mg
                                  1500 mg
                                                                                           7   3
                                                   2.6


                   10             3         25                               3
            29


                                                       Mrs.Lube   56
                   68
                                                       Mrs.Lube                     Mr.Lube




         1000 mg                                                                           1000
                                                  mg                   Mr.Lube
KG-135




                        50
&




126                                                                                                127
43                                        68




                        20                                                        PSA   78.4
                             250 mg                          0~4
                  15                               1000 mg          PSA      25
                                                                   2000 mg
                                                      4


                                                             40
              GOT GPT




                   50




                                                                   1500 mg
                                      3-6
                                            2000                       50
KG-135




         mg


              4                         2
&




128                                                                                            129
78
                                                                          700
                                             4.3                       1000 mg
                                                          700   1500              1500
                                   1000 mg         3500                    7000
                                             4.3
         3.4


               48
                                                          50
                    50        20
                         30




               32
KG-135
&




130                                                                                      131
50


              7
KG-135




                  12-15
&




132                       133
135
             134
KG-135   &
55


          55




           4~5   57




         5~6


          45
KG-135
&




136                   137
54




         Rg3   Rg5   Rk1
KG-135
&




138                        139
87




                                    58




                                3
         4


             BUN
                    3   2            80
         4
                            2




               85
KG-135
&




140                                       141
45




                GOT/GPT           140




         GOT    GPT    40


                  57




          GOT    GPT        400
                                  GOT   GP




                  45
KG-135
&




142                                          143
48




                          60




         GOT        GPT        400
                                           GOT   GPT   400
          100                    42   37                         29


                          60
                                                             2    3


                                                                 100mg
               96    11
KG-135




                     B
&




                                                        B
144                                                                      145
GOT   GPT




                GOT GPT
         1 mg




         1.
         2.
KG-135




         3.
         4.
         5.
&




146                                   147
33


                  25   23




         8




                            55




             30
KG-135
&




148                              149
58




         55
KG-135




                4~5
&




              5~6
150                   151
55


                                 60
              30
                                      60          B      150


                   150


         54                                 150    100


                                 55




                                           10
                                                  360


                     330   280   200                     168
                     200
KG-135
&




152                                                            153
60




         15%~20%




                   72




                   60
KG-135
&




154                     155
55




         60




              1-2
KG-135
&




156                 157
55




                           10
                                360
                                                 36   72
         330   280   200              168
         200


                      55




                                            11
KG-135




                                        30
&




158                                                        159
60
                                         B       B




                       96     11




                       B
                                             2
         B


                       55


                                   160


                            170
             120-140
KG-135
&




160                                                  161
40
                           26




                                1




         30




              5   6
KG-135




         35


                      45
&




162                                 163
32
KG-135
&




164           165
Part   5

       Q&A




166              167
Q
      A                            B.C.
          180




                             113
                21   18.6%




      Q
      A




                                          Q&A
168                                       169
Q


                   Eurekatert        A
                          Guardian   1.




                                     2.
         Q
         A                           3.
                                     4.




                                     Q
         Q
         A                           A


             95%
KG-135
&




                                          Q&A
170                                       171
Q
         A




                         Q


         Q               A
         A               1.
             1           2.
             2           3.
             3           4.
                 1   2
             3


                         Q
                         A
KG-135




         Q
         A
&




                              Q&A
172                           173
Q
         Q
         A                                 A




         Q                                 Q
         A                                 A




         Q


         A
KG-135




                   5   /1
                                 60
             300                           Q
&




                            55             A




                                               Q&A
174                                   27       175
Q
             A




         Q   Q
         A
             A


                       50%


                 20%         30




             Q
             A
KG-135
&




                                  Q&A
176                               177
Q                                            Q
         A                                            A

                                   30            30
                       1
         1-7
                       1            1
                                                                              1
         1-7
                       1            1             1          30
         1-7
                       2            1        1
                                                      Q
         1-7
                       2            2        1
                                                      A
         1-7
                       2            2             2
                                                          500C.C.
         1-7


         Q
                                                                    500C.C.



               700mg       480mg        500mg
                                                      Q
               500mg       254mg        100mg
KG-135




               11          11           11            A
&




                                                                                  Q&A
178                                                                               179
Q
         Q           A


         A


                         5-20
KG-135




                     Q
                     A
&




             1   2




                                Q&A
180                             181
Q
                  A




         Q
         A
             1.   Q
             2.   A
             3.




                  Q
                  A
                                   BUN
                      Creatinine
KG-135




         Q
         A
                  Q
&




                                         Q&A
182               A                      183
Q
             A




             Q
             A




         Q


         A   Q
             A




             Q
KG-135




             A
&




                 Q&A
184              185
Q
         A




         Q
             Q
         A   A




             Q
KG-135




         Q
         A   A   Ginsenoside Rg3
&




                                   Q&A
186                                187
Q
         A
             Q
             A




             Q


             A




         Q
             Q
         A   A
             1.
KG-135




             2.


             3.
&




                  Q&A
188               189
4.




         Q
         A
         1.




         2.   15


                   15


         3.
KG-135




         4.
&




                        Q&A
190                     191
192
KG-135   &

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KG-135 Document Provides Overview of Ginseng Compounds

  • 2. CONTENTS 13 21 KG-135 & 15 Agape Medicine 2011 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. 17 Printed in Taiwan. 19 KG-135 & 2011.05 192 21X15 ISBN 978–986–6552–86–1 1. 2. 3. 414.34 100008505 主編 詹治東 監修 詹瑩璽 審訂 朴萬基、朴政一 出版發行 唐山出版社|Tonsan Publications Inc. 23 10647 臺北市大安區羅斯福路三段333巷9號B1 tel 02–2363–3072 fax 02–2363–9735 tonsan@ms37.hinet.net http://blog.yam.com/tsbooks/  出版日期 2011.05 2 定價 NT $ 250 3
  • 3. Part 1 Part 2 27 55 11 31 57 7 7 34 39 79 4 DNA 47 4 5
  • 4. Part 3 116 KG-135 85 KG-135 KG-135 89 KG-135 KG-135 KG-135 124 100 KG-135 Part 4 113 115 6 7
  • 5. Part 5 Q&A 176 177 169 170 178 171 179 172 180 173 181 182 174 183 175 8 9
  • 6. 184 185 186 187 188 189 190 10 11
  • 7. 2010 12 13
  • 8. Agape Medicine 2008 1 1 40-70 Agape Medicine 4% dark material 23% dark energy 73% KG-135 & Agape 14 15
  • 9. do no harm do harm KG-135 & 16 17
  • 10. 1995 9 11 50 40-70 KG-135 10-30 70 10 & 18 19
  • 11. 20 2000 12 10 2005 2010 KG-135 & 20 21
  • 12. Ginsenoside Rs3 Rs4 7 Rk1 Rg3 Rg5 22 23
  • 13. 1. 2. 3. 4. Part 1 KG-135 & 24 25
  • 14. DNA 26 27
  • 15. . D. Dr. Ernst. D. Prinzenberg Ginsenosides Ra1 Ra2 Ra3 Rb1 Rb2 Rb3 Rc Panaxdiolegroup Rd Rg3 Rh2 Rs1 Rs2 Ginsenosides Panaxtriolegroup Re Rf Rg1 Rg2 Rh1 Rh 3 Ginsenosides Ro O leanolicacid Phenoles Maltol B-12,folic acid, nicotine acid, pantothenic acid, biotin, nicthlamide Aspartic acid, blycine, alanine, praline, valine, isoleucine, tyrosine, phenylalanine, fatty amino acids, arginine 20 200 0.05% KG-135 & 28 29
  • 16. / / panax panacea KG-135 & 30 31
  • 17. 1 2 6000 300 3 4 5 6 7 8 7 1 2 3 4 5 6 KG-135 7 & 32 33
  • 18. 6 10 36 38 KG-135 & 34 35
  • 19. + +++ + +++ + ++ + ++ + +++ + ++ + ++ + +++ + ++ KG-135 3 4 5 6 1.83% 2.09% 2.32% 3.43% 1.59% 1.95% 2.30% 2.79% & 36 37
  • 20. * M.Kiura * W.Petkov * J.Ishigami * DNA M.Yamamoto * H.G. Chai * I.Murata 1960 * S.Odashima * H.Oura * M.Yamamoto * C.N. Joo * B.H. Han I.I. Brekhman 1969 * S.J.Fulder * E.V.Avakian * E.Bombardelli * D.J. Lee * I.Murata * M.Yonezawa N.Saito * Subhuti 6% * Dharemanda * C.N. Joo * J.B. Kim KG-135 * H.Matsuda * T.Saito * V.D.Petkov * O.Tanaka & * S.K.F.Chong * Masao Haneda 38 Shojvo Ikematsu 39
  • 21. 40 R 3O OH R 1O R2 Ginsenoside R1 R2 R3 Rb1 Glc-Glc- H Glc-Glc- Rb2 Glc-Glc- H Ara(p)-Glc- Rc Glc-Glc- H Ara(f)-Glc- Rd Glc-Glc- H Glc- Rg3 Glc-Glc- H H 100 Rs3 Ac-Glc-Glc- H H Re H Rha-Glc-O- H 100 100 Rg1 H Glc-O- Glc- Rg2 H Rha-Glc-O- H Rf H Glc-Glc-O- H Rh1 H Glc-O- H KG-135 & 40 41
  • 22. Rg3 Ginsana 10 Rg3 1 Ginsana G115 Pharmaton Ginsana Ginsana 1 KG-135 & 42 43
  • 23. Rh2 Rg3 Rk1 Rk1 Drug Rk1 Taxol Cell line (μg/ml) (μg/ml) SK-OV-3(卵巢癌細胞) 3.9 ± 0.80 2.3 ± 0.37 NIH:OVCAR-3 (卵巢癌細胞) 18.9 ± 0.21 10.5 ± 3.58 DU-145(攝護腺癌細胞) 21.0 ± 4.24 12.5 ± 2.12 PC-3 (攝護腺癌細胞) 19.0 ± 2.83 4.0 ± 2.80 MCF-7(乳癌細胞) 24.0 ± 0.00 25.5 ± 0.71 HL-60(骨髓性白血病) 5.2 ± 0.08 2.7 ± 0.46 500 1 KG-135 37 1 1 & 44 45
  • 24. Saponin 37 22 14 15 7.47% 3.16% 2.09% 2.25% Rb1 Rb1 Rb1 Rc Rb1 Rb1 Rb Rg1 Rb1 Re DNA RNA Rh2 Rh3 Rg3 Rg2 Rh1 Rg3 1995 Rg1 Re Rd Rg1 11 Rb1 Rb2 Rc Re KG-135 Rg1 Rb1 & 46 5% 100 47
  • 25. 11 500 70 10 40-70 10-30 p.50 p.51 5 100 5 995 KG-135 95% & 48 49
  • 26. 1987 1987-1989 NIH Northwestern University 1977 University of Wisconsin-Madison 1987 University of Pittsburgh 1986-1990 Wurzburg KG-135 1987 1993 & ( ) 50 51 1987 2001
  • 27. 1 Anti-oxidant activity SG 0.8 100 WG 0.6 survival 80 0.4 0.2 2 % Inhibition 60 0 Part 0 200 400 600 800 1000 40 Co n c .(mg /mL) 20 0 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Concentration (mg/mL) 1 Anti-cancer activity SG 0.8 1 WG 0.6 SG survival 0.8 0.4 0.2 WG 0.6 survival 0 0 200 400 600 800 1000 0.4 Co n c .(mg /mL) KG-135 0.2 & 0 0 200 400 600 800 1000 Co n c .(mg /mL) 52 53
  • 28. 11 37 26 11 54 55
  • 29. 7 Major Constitunets Ginsenoside Rk1 Rg3 Rg5 Unique Constituents Ginsenoside Rk2 Rk3 Rg1 Ginsenoside Rs4 Rs5 Rs6 Rs7 Ginsenoside Rh2 11 Rh2 Rg3 Rg1 DNA RNA Rg5,Rk1 Rs3,Rs4 Rg3,Rg5 Rk1 KG-135 & 56 57
  • 30. Antioxidant Activitiy DNA DNA 解毒作用 KG-135 1. 2. & 3. 58 4. 59
  • 31. Chemoprevention Activity 100 80 60 % Inhibition 40 SG RG WG 20 0 0 2 4 6 8 Concentration mg ginseng/mL J. Nat. Prod. 63, 1702 2000 Cancer Letters 150, 41 2000 KG-135 & 60 61
  • 32. 致癌物 1~2 days 1- 排出體外 >10 years 2- 1-解毒癌變物質 促進 >1 year 癌化前細胞 4 4- 1. 2. 3. 腫瘤細胞 3- KG-135 4. & Apoptosis 62 63
  • 33. Anticancer Activity 1 0.8 60~120 0.6 SG Survival RG 0.4 WG 0.2 0 0 200 400 600 800 1000 Concentration mg ginseng/mL Rg3 Rg5 Rk1 Rs4 Rh2 Apoptosis Rg3 Rg5 Rk1 Cancer Letters 150, 41 2000 Anticancer Research 19, 487 1999 Anticancer Research 17, 1067 1997 apoptosis KG-135 & 64 65
  • 34. Control DMBA + TPA 300mg/kg 22 0 1 2 3 22 weeks DMBA TPA TPA TPA TPA TPA TPA TPA TPA Initiation Promotion KG-135 DMBA + TPA HL60 & - - 100 mg/kg - 300 mg/kg 66 67
  • 35. Vascular, relaxation activity 90.0 SG 80.0 RG 70.0 WG 60.0 50.0 40.0 30.0 20.0 10.0 0.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 conc. (-log C) J. Nat. Prod. 63,1702 2000 Eur. J. Pharmacology 367, 41 1999 51 1999 Advances in Ginseng Res. 182 1998 KG-135 & 68 69
  • 36. Rg3 Rg5 Rk1 Kidney protection activity 1.5 150 120 Swimming time min 90 60 KG-135 30 0 Control +Ginseng & Swimming test 70 71
  • 37. 100 mg/kg/day, , 1300 1240 1200 1100 1040 Tumor size Tumor size 1000 890 900 Cisplatin 800 690 Cisplatin BUN 700 Creatinine 600 500 + 100 mg/kg/day, , 90 85 80 Blood cholesterol level mg/dl 1000 Survival day 75 800 70 65 600 60 KG-135 55 400 50 200 45 & 40 0 Control +Ginseng + 72 73
  • 38. Anti-platelet Aggregation 4 3.5 Rg3 3 2.5 2 1.5 1 0.5 0 + control cisplatin cisplatin + 선삼 Rg3 Korean Patent 1998-033461 1998-08-18 Biological Pharmaceutical Bull., 21, 79 1998 Korean J. Ginsengscience, 21, 132 1997 KG-135 & Rg3 74 75
  • 39. Brain Cell Protection Activity Water maze experiment 20 mg/kg, p.o. 7th day 40 35 30 25 20 15 10 5 0 Control SG Passive avoidance test 5 mg/kg, , 7th day SOD 250 200 150 KG-135 100 50 & 0 Control SG Rg3 76 77
  • 40. 100 4 70 50 20 10 Acetylcholine 9 8 7 Concentration ng/mg 6 5 4 3 2 1 0 Control 鉆葚 KG-135 After oral administration for 7 days, 50 mg/kg. Acetylcholine concentration in Hippocampus & 78 79
  • 41. DNA 99.5% Saponin soap DNA 92% 30 50 70 KG-135 & 80 81
  • 42. Part 3 KG-135 82 83
  • 43. KG-135 KG-135 KG-135 KG135 Rk1 Rg3 Rg5 HPLC data Rg1,Re Rb1 Rb2 Rd White Ginsneg Rc Red Ginseng Rg3 Rk1 Rg5 S.G. KG-135 84 85
  • 44. KG-135 1.4 1.2 KG-135 1 Rg3 Rg3 Rg5 Rg5 survival Rk1 0.8 Rk1 0.6 MTT 0.4 1.2000 0.2 1.0000 0.8000 0 0 20 40 60 80 100 0.6000 Concentration (mg/mL) (mg/mL) Survival 0.4000 0.2000 Rs3 Rs4, Rs5 0.0000 0.00 2.75 5.50 8.25 11.00 13.75 16.50 19.25 22.00 24.75 27.50 30.25 33.00 35.75 38.50 41.25 44.00 46.75 49.50 Time min. HPLC separation – Fraction collection – MTT assay KG-135 & KG-135 86 KG-135 87
  • 45. KG-135 CH2 CH CH (C C)2 (X) (CH2)6CH3 R Polyacetylene O OH HO OH KG-135 O Maltol Ginsenoside Rg3 Glc Glc O Ginsenoside Rg5 KG-135 OH Ginsenoside Rk1 & KG-135 Glc Glc O 88 89
  • 46. PC-3 Morphology of PC-3 SP cells 200 X 400 X KG-135 PC-3 PC- 3 KG-135 PC-3 Effect of KG135 on cell viability of PC-3 prostate cells 100 24 h Cell viability (% of control) 48 h 80 72 h 60 40 KG-135 20 0 & 0 2 5 10 20 40 50 60 80 100 KG-135 Concentration (mg/ml) 90 91
  • 47. KG-135 PC- 3 KG135 inhibited PC-3 cell migration Effects of KG135 on side population of PC-3 prostate cells Control 5 g/ml KG135 1.1% 0.4% KG135 PC – 3 7.5 g/ml KG135 +25 mM Verapamil 0.2% 10 g/ml KG135 Side population 1.1 % 5 + 25 mM Reserpine mg/ml KG-135 0% KG-135 0% KG-135 & KG-135 92 93
  • 48. KG-135 Apoptosis KG-135 Apoptosis Autophagy KG-135 & KG-135 94 http://www.nature.com/onc/journal/v23/n16/images/1207521f4.jpg 95
  • 49. Apoptosis inducing effect of KG-135 KG-135 Hydroxychloroquine A549 SKOV-3 Western blot ananysis of A549 human lung cancer cells treated with KG135 for 72 h 4.88% 27.55% 6.44% KG 135 g/ml Control 50 75 100 Control Control 10 m 10 g/ml g/ml 30 30mg/ml g/ml FAK KG135 A549 p-FAK Akt NIH:OVCAR3 LC3-II LC3-I LC3-I KG-135 LC3-II 10.03% 29.04 14.18% % GAPDH KG-135 Control 10 g/ml 20 g/ml & KG-135 96 97
  • 50. Western blot ananysis of A549 human lung cancer cells 3 treated with KG135 for 72 h A549 lung cancer cells 3 days of treatment A549 KG135 50 g/ml KG135 Hydroxychloroquine 25 M A549 FAK p-FAK Akt Control KG135 75 g/ml LC3-II LC3-I LC3-I KG-135 LC3-II GAPDH H-CQ 25 KG135 75 g/ml+H-CQ 25 M KG-135 & KG-135 KG135 98 A549 KG-135 99
  • 51. KG-135 DBTRG 05MG glioblastoma cells 72 h treatment H-CQ KG-135 Hydroxychloroquine DBTRG05MG KG-135 Hydroxychloroquine KG135 DBTRG05MG DBTRG 05MG DBTRG 05MG glioblastoma cells 72 h treatment H-CQ KG-135 & KG135 KG-135 DBTRG 05MG 100 KG-135 101
  • 52. KG-135 matformin KG-135 A549 Chemoprevention activity KG-135 matformin A549 01/24 DMBA + TPA DMBA + TPA+ 100 mg KG135 metformin A549 KG-135 DMBA + TPA+ 500 mg & KG-135 102 103
  • 53. KG-135 Standardized SG extract inhibits TPA- Effects of KG-135 on phorbol ester-induced cox-2 induced COX-2 expression in human breast epithelial expression and ERK activation in mouse skin MCF-10A cells. + KG-135 mg/kg 0 100 500 KG-135 Control + TPA TPA COX-2 COX-2 Actin Actin pERK KG-135 TPA COX-2 ERK Gapdh KG-135 inhibits cox-2 expression and ERK activation KG-135 inhibits TPA-induced cox-2 expression in MCF-10A cells KG-135 COX-2 + TPA COX-2 + TPA KG-135 & KG-135 KG-135 104 105
  • 54. Effect of KG-135 on TPA-Induced Subsequent Degradation of Icy-a, and on NF-kB DNA Binding in Mouse Skin Treated with TPA 120 + KG-135 mg/kg 0 100 500 100 Control + TPA % Mice with tumors Control IkB-a 80 Control+SG 100mg/kg 60 Control+SG 500mg/kg IkB-a 40 20 Control_negative Actin 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Weeks IkB-a NF-kB TPA + Co only KG-135(mg/kg) l ro p. e A ob nt m TP 0 KG-135 0 Co 50 Pr 10 KG-135 NF-kB & KG-135 106 107
  • 55. KG-135 SG-unique constituents inhibits COX-2 expression KG-135 inhibits BrDU and PCNA in vivo by blocking the activation of JNK and AP-1 in phorbol ester- DMBA + TPA stimulated human breast epithelial cells. KG-135 KG-135 Control Acetone DMBA + TPA 100mg/kg 500mg/kg KG-135 TPA JNK JNK BrDU KG-135 KG-135 JNK KG-135 KG-135 on obe KG-135 - - + pr ld e pr ly ob TPA - - co + + + AP-1 PCNA 激活蛋 白 KG-135 & KG-135 108 109
  • 56. 100 DMBA-TPA 80 + 0.1% SG % Tumor bearing mice 60 + 0.5% SG Part 4 40 20 0 0 2 4 6 8 10 12 14 16 18 20 22 Week Cancer Letters, 150, 41 2000 Topical application of SG 10 min prior to TPA application KG-135 & 110 111
  • 57. 1. 2. 3. 112 113
  • 58. 1. 2. 3. 2005 KG-135 & 114 115
  • 59. 100mg 200mg 5~7 250mg 250mg 500 mg 1000mg 15 KG-135 & 116 117
  • 60. KG-135 3 & 118 119
  • 61. 11. 12. 1. 13. 14. 2. 15. 3. 16. 17. 4. 18. 19. 5. 20. 6. 21. 7. 22. 8. 23. 9. KG-135 45. 10: 25. & 26. 120 121
  • 62. 27. 42. 28. 43. 29. 44. 30. 45. / 31. 32. 33. 34. 35. 36. 37. 38. KG-135 39. 40. & 41. 122 123
  • 63. 54 60 55 76 KG-135 1000 mg & 124 125
  • 64. 59 15 1000 mg 25 1500 mg 1500 mg 7 3 2.6 10 3 25 3 29 Mrs.Lube 56 68 Mrs.Lube Mr.Lube 1000 mg 1000 mg Mr.Lube KG-135 50 & 126 127
  • 65. 43 68 20 PSA 78.4 250 mg 0~4 15 1000 mg PSA 25 2000 mg 4 40 GOT GPT 50 1500 mg 3-6 2000 50 KG-135 mg 4 2 & 128 129
  • 66. 78 700 4.3 1000 mg 700 1500 1500 1000 mg 3500 7000 4.3 3.4 48 50 50 20 30 32 KG-135 & 130 131
  • 67. 50 7 KG-135 12-15 & 132 133
  • 68. 135 134 KG-135 &
  • 69. 55 55 4~5 57 5~6 45 KG-135 & 136 137
  • 70. 54 Rg3 Rg5 Rk1 KG-135 & 138 139
  • 71. 87 58 3 4 BUN 3 2 80 4 2 85 KG-135 & 140 141
  • 72. 45 GOT/GPT 140 GOT GPT 40 57 GOT GPT 400 GOT GP 45 KG-135 & 142 143
  • 73. 48 60 GOT GPT 400 GOT GPT 400 100 42 37 29 60 2 3 100mg 96 11 KG-135 B & B 144 145
  • 74. GOT GPT GOT GPT 1 mg 1. 2. KG-135 3. 4. 5. & 146 147
  • 75. 33 25 23 8 55 30 KG-135 & 148 149
  • 76. 58 55 KG-135 4~5 & 5~6 150 151
  • 77. 55 60 30 60 B 150 150 54 150 100 55 10 360 330 280 200 168 200 KG-135 & 152 153
  • 78. 60 15%~20% 72 60 KG-135 & 154 155
  • 79. 55 60 1-2 KG-135 & 156 157
  • 80. 55 10 360 36 72 330 280 200 168 200 55 11 KG-135 30 & 158 159
  • 81. 60 B B 96 11 B 2 B 55 160 170 120-140 KG-135 & 160 161
  • 82. 40 26 1 30 5 6 KG-135 35 45 & 162 163
  • 84. Part 5 Q&A 166 167
  • 85. Q A B.C. 180 113 21 18.6% Q A Q&A 168 169
  • 86. Q Eurekatert A Guardian 1. 2. Q A 3. 4. Q Q A A 95% KG-135 & Q&A 170 171
  • 87. Q A Q Q A A 1. 1 2. 2 3. 3 4. 1 2 3 Q A KG-135 Q A & Q&A 172 173
  • 88. Q Q A A Q Q A A Q A KG-135 5 /1 60 300 Q & 55 A Q&A 174 27 175
  • 89. Q A Q Q A A 50% 20% 30 Q A KG-135 & Q&A 176 177
  • 90. Q Q A A 30 30 1 1-7 1 1 1 1-7 1 1 1 30 1-7 2 1 1 Q 1-7 2 2 1 A 1-7 2 2 2 500C.C. 1-7 Q 500C.C. 700mg 480mg 500mg Q 500mg 254mg 100mg KG-135 11 11 11 A & Q&A 178 179
  • 91. Q Q A A 5-20 KG-135 Q A & 1 2 Q&A 180 181
  • 92. Q A Q A 1. Q 2. A 3. Q A BUN Creatinine KG-135 Q A Q & Q&A 182 A 183
  • 93. Q A Q A Q A Q A Q KG-135 A & Q&A 184 185
  • 94. Q A Q Q A A Q KG-135 Q A A Ginsenoside Rg3 & Q&A 186 187
  • 95. Q A Q A Q A Q Q A A 1. KG-135 2. 3. & Q&A 188 189
  • 96. 4. Q A 1. 2. 15 15 3. KG-135 4. & Q&A 190 191